Influence of dosimetry accuracy on the correlation with treatment outcome in a preliminary PSMA radiopharmaceutical therapy study

Abstract Introduction Despite the potential of dosimetry in optimizing personalized radiopharmaceutical therapy (RPT), its limited clinical implementation impedes the development of simplified protocols for routine adoption. However, simplifications may introduce errors in dosimetry, prompting questions about their impact on clinical practice. Materials and methods In this retrospective study, we analyzed data from 21 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) who underwent multiple cycles of 177 Lu-PSMA-617 RPT treatment. Cumulative dosimetry of all the treatment cycles was calculated using both the standard multi-time point dosimetry (MTPD) method and the single time-point dosimetry (STPD, Hänscheid approximation) method for the same cohort. Their correlations with treatment outcome (PSA decline rate and overall survival, OS) and complication risk (anaemia grade) were investigated. The Fisher's Z-Transformed test was performed to statistically evaluate the difference between the correlations. Results STPD showed a non-significant difference in correlation with PSA decline rate, despite a mean percentage error (MPE) of up to 36.44% in tumor dosimetry compared to MTPD (MTPD: rho = -0.39, p < 0.001; STPD: rho = -0.46, p < 0.001; Z = 0.58, p = 0.56). Both STPD total and MTPD total demonstrated a significant impact on OS (STPD total : Hazard Ratio = 1.05, p < 0.05, log-transformed MTPD total : Hazard Ratio = 3.41, p < 0.05, log-transformed STPD total : Hazard Ratio = 8.06, p < 0.05). Additionally, despite a MPE of up to -40.26% in bone marrow dosimetry, STPD showed a non-significant difference in correlation with anemia grade (MTPD: rho = 0.35, p < 0.001; STPD: rho = 0.40, p < 0.001; Z = -0.39, p = 0.70). Conclusion The preliminary findings from a small cohort indicate that the reduced accuracy of a clinically simplified protocol may not diminish the clinical therapy outcome predictive value of dosimetry. Future thorough systematic investigations may be needed to determine the clinically acceptable level of accuracy for dosimetry.